Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome

Clin Endocrinol (Oxf). 2001 Mar;54(3):335-8. doi: 10.1046/j.1365-2265.2001.01230.x.


Objective: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare systemic autoimmune disorder of monogenic and autosomal-recessive inheritance. To date, 29 APECED causing mutations have been identified in the responsible gene AIRE-1, coding for a regulator of transcription. The aim of this study was to examine whether mutations in AIRE-1, in their heterozygous form, predispose to the more common isolated autoimmune endocrinopathies Addison's disease, type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis.

Design: Patients with isolated autoimmune endocrine disorders as well as healthy controls were analysed for two of the most common AIRE-1 mutations, mutation R257X in exon 6 and a 13-bp deletion in exon 8. Mutations were detected by polymerase chain reaction based techniques.

Patients: In total, 726 individuals were investigated for mutation R257X. Subjects comprised patients with Addison's disease, IDDM, Graves' disease and Hashimoto's thyroiditis. With regard to the 13 bp deletion we could screen 91 patients with Addison's disease. In addition, six patients with the APECED syndrome including one family were analysed for both mutations.

Results: Out of the 12 alleles in APECED patients six contained either mutation R257X or the 13 bp deletion, confirming that these mutations prevail in Europe. R257X was found in one subject with Hashimoto's thyroiditis in its heterozygous form. The 13 bp deletion was not detected in any subject with Addison's disease.

Conclusions: The two studied AIRE-1 mutations are so rare in the general population that they can not contribute to susceptibility for the more common isolated autoimmune disorders.

MeSH terms

  • Addison Disease / genetics*
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 1 / genetics*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Graves Disease / genetics*
  • Humans
  • Polyendocrinopathies, Autoimmune / genetics*
  • Thyroiditis, Autoimmune / genetics*
  • Transcription Factors / genetics*


  • APECED protein
  • Transcription Factors